Asymptomatic high flow subclavian steal in a patient with hemodialysis access.

Subclavian steal phenomenon due to proximal subclavian artery stenosis or occlusion is not un-common but often remains asymptomatic. We describe the case of a 66-year-old man with end-stage renal disease hemodialysed through a brachio-brachial loop graft of the left forearm. Echo-Doppler precerebral examination showed a high reversed flow of 570 ml/min in the ipsilateral vertebral artery. After successful endovascular recanalization of the subclavian artery, access blood flow increased and vertebral flow decreased to 30 ml/min. Complete neurological examination was normal both before and after endovascular treatment. This case demonstrates how high a subclavian steal can be without causing symptoms and how well precerbral and cerebral circulation can adapt to hemodynamic changes.

Transfer insensitive labeling technique (TILT): application to multislice functional perfusion imaging.

Cerebral blood flow can be studied in a multislice mode with a recently proposed perfusion sequence using inversion of water spins as an endogenous tracer without magnetization transfer artifacts. The magnetization transfer insensitive labeling technique (TILT) has been used for mapping blood flow changes at a microvascular level under motor activation in a multislice mode. In TILT, perfusion mapping is achieved by subtraction of a perfusion-sensitized image from a control image. Perfusion weighting is accomplished by proximal blood labeling using two 90 degrees radiofrequency excitation pulses. For control preparation the labeling pulses are modified such that they have no net effect on blood water magnetization. The percentage of blood flow change, as well as its spatial extent, has been studied in single and multislice modes with varying delays between labeling and imaging. The average perfusion signal change due to activation was 36.9 +/- 9.1% in the single-slice experiments and 38.1 +/- 7.9% in the multislice experiments. The volume of activated brain areas amounted to 1.51 +/- 0.95 cm3 in the contralateral primary motor (M1) area, 0.90 +/- 0.72 cc in the ipsilateral M1 area, 1.27 +/- 0.39 cm3 in the contralateral and 1.42 +/- 0.75 cm3 in the ipsilateral premotor areas, and 0.71 +/- 0.19 cm3 in the supplementary motor area.

Effets de la perfusion de facteurs natriurétiques auriculaires synthétiques sur quelques flux régionaux chez le volontaire sain [Effect of synthetic atrial natriuretic factors on various regional blood flows in the healthy subject]

The effects of continuous infusions of 2 synthetic atrial natriuretic peptides Ile12-(3-28) (rANP) and Meth12-(3-28) (hANP) eicosahexapeptides on blood pressure, heart rate, skin blood flow, glomerular filtration rate, renal plasma flow, apparent hepatic blood flow, and carotid blood flow were evaluated in normal volunteers. A rANP infusion at increasing rates (1-40 micrograms/min) induced a decrease in blood pressure, an increase in heart rate and in skin blood flow linearly related to the dose administered. In contrast, hANP infusion at 1 microgram/min for 4 hours induced an initial increase followed by a secondary fall in skin blood flow without blood pressure changes. A 4-hour rANP infusion at 0.5 and 5 mcg/min did not alter glomerular filtration rate but induced a delayed and dose-related fall in renal plasma flow from 531 to 461 (p less than 0.05), and from 554 to 342 ml/min (p less than 0.001) respectively, with a consequential rise in the filtration fraction. The 5 mcg/min dose furthermore significantly reduced blood pressure following a latency period of 2.5 hours. A 2-hours rANP infusion at 0.5 micrograms/min induced a fall in apparent hepatic blood flow from 1,087 to 863 ml/min (p less than 0.01), without simultaneously altering blood pressure. Similarly, a 2-hour hANP infusion at 2 micrograms/min altered neither blood pressure nor carotid blood flow. In conclusion, ANP infusion induced changes in systemic and regional hemodynamics varying in direction, intensity and duration.

Flow targeted 3D steady-state free-precession coronary MR angiography: comparison of three different imaging approaches.

PURPOSE: To compare 3 different flow targeted magnetization preparation strategies for coronary MR angiography (cMRA), which allow selective visualization of the vessel lumen. MATERIAL AND METHODS: The right coronary artery of 10 healthy subjects was investigated on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Healthcare, Best, NL). A navigator-gated and ECG-triggered 3D radial steady-state free-precession (SSFP) cMRA sequence with 3 different magnetization preparation schemes was performed referred to as projection SSFP (selective labeling of the aorta, subtraction of 2 data sets), LoReIn SSFP (double-inversion preparation, selective labeling of the aorta, 1 data set), and inflow SSFP (inversion preparation, selective labeling of the coronary artery, 1 data set). Signal-to-noise ratio (SNR) of the coronary artery and aorta, contrast-to-noise ratio (CNR) between the coronary artery and epicardial fat, vessel length and vessel sharpness were analyzed. RESULTS: All cMRA sequences were successfully obtained in all subjects. Both projection SSFP and LoReIn SSFP allowed for selective visualization of the coronary arteries with excellent background suppression. Scan time was doubled in projection SSFP because of the need for subtraction of 2 data sets. In inflow SSFP, background suppression was limited to the tissue included in the inversion volume. Projection SSFP (SNR(coro): 25.6 +/- 12.1; SNR(ao): 26.1 +/- 16.8; CNR(coro-fat): 22.0 +/- 11.7) and inflow SSFP (SNR(coro): 27.9 +/- 5.4; SNR(ao): 37.4 +/- 9.2; CNR(coro-fat): 24.9 +/- 4.8) yielded significantly increased SNR and CNR compared with LoReIn SSFP (SNR(coro): 12.3 +/- 5.4; SNR(ao): 11.8 +/- 5.8; CNR(coro-fat): 9.8 +/- 5.5; P < 0.05 for both). Longest visible vessel length was found with projection SSFP (79.5 mm +/- 18.9; P < 0.05 vs. LoReIn) whereas vessel sharpness was best in inflow SSFP (68.2% +/- 4.5%; P < 0.05 vs. LoReIn). Consistently good image quality was achieved using inflow SSFP likely because of the simple planning procedure and short scanning time. CONCLUSION: Three flow targeted cMRA approaches are presented, which provide selective visualization of the coronary vessel lumen and in addition blood flow information without the need of contrast agent administration. Inflow SSFP yielded highest SNR, CNR and vessel sharpness and may prove useful as a fast and efficient approach for assessing proximal and mid vessel coronary blood flow, whereas requiring less planning skills than projection SSFP or LoReIn SSFP.

Proximal sodium reabsorption: An independent determinant of blood pressure response to salt.

The purpose of this study was to evaluate the contribution of renal sodium handling by the proximal tubule as an independent determinant of blood pressure responsiveness to salt in hypertension. We measured blood pressure (BP), renal hemodynamics, and segmental renal sodium handling (with lithium used as a marker of proximal sodium reabsorption) in 38 hypertensive patients and 27 normotensive subjects (15 young and 12 age-matched) on a high and low sodium diet. In control subjects, changing the diet from a low to a high sodium content resulted in no change in BP and increases in glomerular filtration rate (P<0.05), renal plasma flow (P<0.05), and fractional excretion of lithium (FE(Li), P<0.01). In hypertensive patients, comparable variations of sodium intake induced an increase in BP with no change in renal hemodynamics and proximal sodium reabsorption. When analyzed by tertiles of their BP response to salt, salt-insensitive hypertensive patients of the first tertile disclosed a pattern of adaptation of proximal sodium reabsorption comparable to that of control subjects, whereas the most salt-sensitive patients of the third tertile had an inverse pattern with a high FE(Li) on low salt and a lower FE(Li) on high salt, suggesting an inappropriate modulation of proximal sodium reabsorption. The BP response to salt correlated positively with age (r=0.34, P=0.036) and negatively with the changes in FE(Li) (r=-0.37, P=0.029). In a multivariate analysis, the changes in FE(Li) were significantly and independently associated with the salt-induced changes in BP. These results suggest that proximal sodium reabsorption is an independent determinant of the BP response to salt in hypertension.

Calcium entry blockade attenuates the acute blood pressure rise induced by cigarette smoking.

The purpose of this study was to assess whether the administration of a calcium entry blocker can prevent the acute blood pressure rise induced by cigarette smoking. Seven male habitual smokers were included. After 45 min of equilibration, they took in randomized single-blind fashion at a 1 week interval either a placebo or nifedipine, 10 mg p.o. Thirty minutes thereafter, the subjects smoked within 10 min two cigarettes containing 1.4 mg of nicotine each. In addition to heart rate and skin blood flow (laser Doppler method), blood pressure of the median left finger was monitored continuously for 100 min using a noninvasive device (Finapres). Nifedipine induced an increase in skin blood flow that was not influenced by smoking. This skin blood flow response was observed although nifedipine had by itself no effect on systemic blood pressure. The calcium antagonist markedly attenuated the blood pressure rise induced by cigarette smoking. However, it tended to accentuate the heart rate acceleration resulting from inhalation of nicotine-containing smoke.

Flow-targeted inversion-prepared b-TFE coronary MR angiography: initial results in patients.

PURPOSE: Visualization of coronary blood flow in the right and left coronary system in volunteers and patients by means of a modified inversion-prepared bright-blood coronary magnetic resonance angiography (cMRA) sequence. MATERIALS AND METHODS: cMRA was performed in 14 healthy volunteers and 19 patients on a 1.5 Tesla MR system using a free-breathing 3D balanced turbo field echo (b-TFE) sequence with radial k-space sampling. For magnetization preparation a slab selective and a 2D selective inversion pulse were used for the right and left coronary system, respectively. cMRA images were evaluated in terms of clinically relevant stenoses (< 50 %) and compared to conventional catheter angiography. Signal was measured in the coronary arteries (coro), the aorta (ao) and in the epicardial fat (fat) to determine SNR and CNR. In addition, maximal visible vessel length, and vessel border definition were analyzed. RESULTS: The use of a selective inversion pre-pulse allowed direct visualization of the coronary blood flow in the right and left coronary system. The measured SNR and CNR, vessel length, and vessel sharpness in volunteers (SNR coro: 28.3 +/- 5.0; SNR ao: 37.6 +/- 8.4; CNR coro-fat: 25.3 +/- 4.5; LAD: 128.0 cm +/- 8.8; RCA: 74.6 cm +/- 12.4; Sharpness: 66.6 % +/- 4.8) were slightly increased compared to those in patients (SNR coro: 24.1 +/- 3.8; SNR ao: 33.8 +/- 11.4; CNR coro-fat: 19.9 +/- 3.3; LAD: 112.5 cm +/- 13.8; RCA: 69.6 cm +/- 16.6; Sharpness: 58.9 % +/- 7.9; n.s.). In the patient study the assessment of 42 coronary segments lead to correct identification of 10 clinically relevant stenoses. CONCLUSION: The modification of a previously published inversion-prepared cMRA sequence allowed direct visualization of the coronary blood flow in the right as well as in the left coronary system. In addition, this sequence proved to be highly sensitive regarding the assessment of clinically relevant stenotic lesions.

Superior flow for bridge to life with self-expanding venous cannulas.

BACKGROUND: Recently, a compact cardiopulmonary support (CPS) system designed for quick set-up for example, during emergency cannulation, has been introduced. Traditional rectilinear percutaneous cannulas are standard for remote vascular access with the original design. The present study was designed to assess the potential of performance increase by the introduction of next-generation, self-expanding venous cannulas, which can take advantage of the luminal width of the venous vasculature despite a relatively small access orifice. METHODS: Veno-arterial bypass was established in three bovine experiments (69+/-10 kg). The Lifebridge (Lifebridge GmbH, Munich, Germany) system was connected to the right atrium in a trans-jugular fashion with various venous cannulas; and the oxygenated blood was returned through the carotid artery with a 17 F percutaneous cannula. Two different venous cannulas were studied, and the correlation between the centrifugal pump speed (1500-3900 RPM), flow and the required negative pressure on the venous side was established: (A) Biomedicus 19 F (Medtronic, Tolochenaz, Switzerland); (B) Smart canula 18 F/36 F (Smartcanula LLC, Lausanne, Switzerland). RESULTS: At 1500 RPM, the blood flow was 0.44+/-0.26 l min(-1) for the 19 F rectilinear cannula versus 0.73+/-0.34 l min(-1) for the 18/36 F self-expanding cannula. At 2500 RPM the blood flow was 1.63+/-0.62 l min(-1) for the 19F rectilinear cannula versus 2.13+/-0.34 l min(-1) for the 18/36 F self-expanding cannula. At 3500 RPM, the blood flow was 2.78+/-0.47 l min(-1) for the 19 F rectilinear cannula versus 3.64+/-0.39 l min(-1) for the 18/36 F self-expanding cannula (p<0.01 for 18/36 F vs 19 F). At 1500 RPM, the venous line pressure was 18+/-8 mmHg for the 19F rectilinear cannula versus 19+/-5 mmHg for the 18/36 F self-expanding cannula. At 2500 RPM the venous line pressure accounted for -22+/-32 mmHg for the 19 F rectilinear cannula versus 2+/-5 mmHg for the 18/36 F self-expanding cannula. At 3500 RPM, the venous line pressure was -112+/-42 mmHg for the rectilinear cannula versus 28+/-7 mmHg for the 18/36 F self-expanding cannula (p<0.01 for 18 F/36 F vs 19 F). Conclusions: The negative pressure required to achieve adequate venous drainage with the self-expanding venous cannula accounts for approximately 31% of the pressure necessary with the 19 F rectilinear cannula. In addition, a pump flow of more than 4 l min(-1) can be achieved with the self-expanding design and a well-accepted negative inlet pressure for minimal blood trauma of less than 50 mmHg.

Brain perfusion in sepsis.

Brain dysfunction is a frequent complication of sepsis, usually defined as "sepsis-associated encephalopathy" (SAE). Its pathophysiology is complex and related to numerous processes and pathways, while the exact mechanisms producing neurological impairment in septic patients remain incompletely elucidated. Alterations of the cerebral blood flow (CBF) may represent a key component for the development of SAE. Reduction of CBF may be caused by cerebral vasoconstriction, either induced by inflammation or hypocapnia. Endothelial dysfunction associated with sepsis leads to impairment of microcirculation and cerebral metabolic uncoupling that may further reduce brain perfusion so that CBF becomes inadequate to satisfy brain cellular needs. The natural autoregulatory mechanisms that protect the brain from reduced/ inadequate CBF can be impaired in septic patients, especially in those with shock or delirium, and this further contributes to cerebral ischemia if blood pressure drops below critical thresholds. Sedative agents alter cerebro-vascular reactivity and may significantly reduce CBF. Although disorders of brain perfusion and alteration of CBF and cerebral autoregulation are frequently observed in humans with sepsis, their exact role in the pathogenesis of SAE remains unknown. Brain perfusion can further become inadequate due to cerebral microcirculatory dysfunction, as evidenced in the experimental setting. Microvascular alterations can be implicated in the development of electrophysiological abnormalities observed during sepsis and contribute to neurological alterations in septic animals. The aim of this review is to provide an update on the pathophysiology of brain perfusion in sepsis, with a particular focus on human clinical investigation and novel tools for CBF monitoring in septic patients.

Microparticles from stored red blood cells induce thrombin generation

Background: Microparticles are small phospholipid vesicles of <1 lm shed in blood flow by various cell types including red blood cells. Erythrocyte-derived microparticles (EMPs) accumulate in erythrocyte concentrates (ECs) during their storage time. EMPs are considered as part of storage lesion and as their exact role is not elucidated, they could be involved in these clinical outcomes. Aims: The aim of this study is to evaluate the impact and implication of EMPs isolate from ECs on coagulation. Methods: EMPs were first isolated from erythrocyte concentrates by centrifugation and counted by flow cytometry. Using a calibrated automated thrombogram, EMPs were then added to different type of plasmas in order to evaluate the potential of thrombin generation. Results: We demonstrate that EMPs isolated from ECs are capable to accelerate and amplify thrombin generation in presence of a low exogenous tissue factor concentration, thanks to their negatively charged membrane necessary for the assembly of coagulation complexes. Interestingly, in the absence of exogenous tissue factor, EMPs are also able to trigger thrombin generation. In addition, thrombin generation induced by EMPs is not affected by the presence of anti-TF antibodies. Finally, thrombin generation induced by EMPs is not affected by using plasma samples deficient in factor VII, XI or XII. However, thrombin generation is reduced in plasma deficient in factor VIII or IX and is completely abolished in plasma deficient in factor X, V or II. No thrombin generation was observed in plasma samples without EMPs. Summary/conclusion: Several studies have shown a link between storage time of blood products and post transfusion complications. We provide evidence that EMPs accumulated during storage of erythrocyte concentrates were not only able to accelerate and support thrombin generation in plasma in presence of a low exogenous tissue-factor concentration, but also to trigger thrombin generation in absence of exogenous TF. The impact of those transfused EMs is unknown on recipients, nevertheless it could be hypothesized that under certain circumstances, transfused EMPs could be involved in thrombin generation and could be linked to adverse clinical outcome. Further work is needed to determine whether procoagulant EMPs transfused with erythrocyte concentrate may account for some of the complications occurring after red blood cell transfusion, and more particularly after transfusion of ''older''stored blood, rich in EMPs.

Desensitization of thermal hyperemia in the skin is reproducible.

OBJECTIVE: Local heating increases skin blood flow SkBF (thermal hyperemia). In a previous study, we reported that a first local thermal stimulus could attenuate the hyperemic response to a second one applied later on the same skin spot, a phenomenon that we termed desensitization. However, other studies found no evidence for desensitization in similar conditions. The aim of the present work was to test whether it was related to differences in instrumentation. METHODS: Twenty-eight healthy young males were studied. Two pairs of heating chambers, one custom-made (our study) and one commercial (other groups), were affixed to forearm skin. SkBF was measured with single-point laser-Doppler flowmetry (LDF) (780nm) in one pair, and laser-Doppler imaging (LDI) (633nm) in the other. A temperature step from 34 to 41°C, was applied for 30minutes and repeated after two hours. RESULTS: During the second thermal challenge, the plateau SkBF was lower than during the first thermal and was observed with each of the four combinations of SkBF measurement techniques and heating equipment (p<0.05 for all conditions, range -9% to -16% of the initial value). CONCLUSION: Desensitization of thermal hyperemia is not specific to peculiar operating conditions.

High-resolution spatial mapping of changes in the neurochemical profile after focal ischemia in mice.

After ischemic stroke, the ischemic damage to brain tissue evolves over time and with an uneven spatial distribution. Early irreversible changes occur in the ischemic core, whereas, in the penumbra, which receives more collateral blood flow, the damage is more mild and delayed. A better characterization of the penumbra, irreversibly damaged and healthy tissues is needed to understand the mechanisms involved in tissue death. MRSI is a powerful tool for this task if the scan time can be decreased whilst maintaining high sensitivity. Therefore, we made improvements to a (1) H MRSI protocol to study middle cerebral artery occlusion in mice. The spatial distribution of changes in the neurochemical profile was investigated, with an effective spatial resolution of 1.4 μL, applying the protocol on a 14.1-T magnet. The acquired maps included the difficult-to-separate glutamate and glutamine resonances and, to our knowledge, the first mapping of metabolites γ-aminobutyric acid and glutathione in vivo, within a metabolite measurement time of 45 min. The maps were in excellent agreement with findings from single-voxel spectroscopy and offer spatial information at a scan time acceptable for most animal models. The metabolites measured differed with respect to the temporal evolution of their concentrations and the localization of these changes. Specifically, lactate and N-acetylaspartate concentration changes largely overlapped with the T(2) -hyperintense region visualized with MRI, whereas changes in cholines and glutathione affected the entire middle cerebral artery territory. Glutamine maps showed elevated levels in the ischemic striatum until 8 h after reperfusion, and until 24 h in cortical tissue, indicating differences in excitotoxic effects and secondary energy failure in these tissue types. Copyright © 2011 John Wiley & Sons, Ltd.

Low-Dose Vascular Photodynamic Therapy Decreases Tumor Interstitial Fluid Pressure, which Promotes Liposomal Doxorubicin Distribution in a Murine Sarcoma Metastasis Model.

INTRODUCTION: Solid tumors are known to have an abnormal vasculature that limits the distribution of chemotherapy. We have recently shown that tumor vessel modulation by low-dose photodynamic therapy (L-PDT) could improve the uptake of macromolecular chemotherapeutic agents such as liposomal doxorubicin (Liporubicin) administered subsequently. However, how this occurs is unknown. Convection, the main mechanism for drug transport between the intravascular and extravascular spaces, is mostly related to interstitial fluid pressure (IFP) and tumor blood flow (TBF). Here, we determined the changes of tumor and surrounding lung IFP and TBF before, during, and after vascular L-PDT. We also evaluated the effect of these changes on the distribution of Liporubicin administered intravenously (IV) in a lung sarcoma metastasis model. MATERIALS AND METHODS: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the lung of Fischer rats. Tumor/surrounding lung IFP and TBF changes induced by L-PDT were determined using the wick-in-needle technique and laser Doppler flowmetry, respectively. The spatial distribution of Liporubicin in tumor and lung tissues following IV drug administration was then assessed in L-PDT-pretreated animals and controls (no L-PDT) by epifluorescence microscopy. RESULTS: L-PDT significantly decreased tumor but not lung IFP compared to controls (no L-PDT) without affecting TBF. These conditions were associated with a significant improvement in Liporubicin distribution in tumor tissues compared to controls (P < .05). DISCUSSION: L-PDT specifically enhanced convection in blood vessels of tumor but not of normal lung tissue, which was associated with a significant improvement of Liporubicin distribution in tumors compared to controls.

Intraoperative cerebral perfusion and postoperative cognitive dysfunction in geriatric patients

Background: Inadequate intraoperative cerebral perfusion has been suggested as a possible cause of postoperative cognitive dysfunction (POCD). Methods: We investigated 35 patients aged 65 or older undergoing elective major non-cardiac surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl, atracurium). Intraoperative cerebral perfusion was monitored with transcranial Doppler, and near-infrared spectroscopy (NIRS). Arterial blood pressure was monitored continuously with a Finapres device. Mx, an index allowing continuous monitoring of cerebrovascular autoregulation based on the changes in mean arterial blood pressure (MAP) and cerebral blood flow velocity was calculated. Mx >0.5 was defined as disturbed cerebrovascular autoregulation. Cognitive function was measured preoperatively and 7 days postoperatively using the CERAD-NAB Plus test battery. A postoperative decline >1 z-score in at least two of the tested domains was defined as POCD. Data are shown as mean } SD. Results: Mean age was 75 } 7 yrs. Sixteen patients (46%) developed POCD. These patients were older (77 } 8 vs 73 } 7 yrs), had lower MAP (77 } 12 vs 81 } 11 mm Hg), lower cerebral tissue oxygenation indices measured by NIRS (66.8 } 6.0 vs 68.6 } 4.3%) and less efficient cerebrovascular autoregulation (Mx 0.54 } 0.17 and 0.44 } 0.22) than patients without POCD. Disturbed intraoperative cerebrovascular autoregulation was found more often (56 vs 37%) in patients with POCD. However, none of these differences reached statistical significance. Conclusions: Our data show a trend towards subtle changes in intraoperative cerebral perfusion in elderly patients who develop POCD. However, a cause effect relationship must not be assumed and a greater number of patients needs to be investigated patients. However, more patients need to be investigated to confirm and characterize these differences.